2. Academic Validation
  3. A small-molecule inhibitor of C5 complement protein

A small-molecule inhibitor of C5 complement protein

  • Nat Chem Biol. 2019 Jul;15(7):666-668. doi: 10.1038/s41589-019-0303-9.
Keith Jendza 1,  Mitsunori Kato 1,  Michael Salcius 2,  Honnappa Srinivas 3,  Andrea De Erkenez 4,  Anh Nguyen 4,  Doug McLaughlin 2,  Celine Be 3,  Christian Wiesmann 3,  Jason Murphy 2,  Philippe Bolduc 1,  Muneto Mogi 1,  Jose Duca 1,  Abdel Namil 1,  Michael Capparelli 1,  Veronique Darsigny 1,  Erik Meredith 1,  Ritesh Tichkule 1,  Luciana Ferrara 4,  Jessica Heyder 4,  Fang Liu 4,  Patricia A Horton 2,  Michael J Romanowski 2,  Markus Schirle 2,  Nello Mainolfi 1,  Karen Anderson 4,  Gregory A Michaud 5
Affiliations

Affiliations

  • 1 Global Discovery Chemistry, Novartis Institutes of Biomedical Research, Cambridge, MA, USA.
  • 2 Chemical Biology and Therapeutics, Novartis Institutes of Biomedical Research, Cambridge, MA, USA.
  • 3 Chemical Biology and Therapeutics, Novartis Institutes of Biomedical Research, Basel, Switzerland.
  • 4 Ophthalmology, Novartis Institutes of Biomedical Research, Cambridge, MA, USA.
  • 5 Chemical Biology and Therapeutics, Novartis Institutes of Biomedical Research, Cambridge, MA, USA. [email protected].
PMID: 31209353 DOI: 10.1038/s41589-019-0303-9
Abstract

The complement pathway is an important part of the immune system, and uncontrolled activation is implicated in many diseases. The human Complement Component 5 protein (C5) is a validated drug target within the complement pathway, as an anti-C5 antibody (Soliris) is an approved therapy for paroxysmal nocturnal hemoglobinuria. Here, we report the identification, optimization and mechanism of action for the first small-molecule inhibitor of C5 complement protein.

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